title: Synthesis of 3-Amino-l-CarboxymethyI-Benzodiazepine (BZA) Peptidomimetics.
abstract: Replacement of key structural or binding elements of a peptide lead with nonpeptide components can improve affinity and metabolic stability (1-5). Such a strategy was successfully applied to the generation of potent, cell-permeable inhibitors of Ras famesyltransferase (FTase) (6,7). The central pair of amino acids in the CAAX tetrapeptide was replaced with the nonpeptide scaffold 3-methylamino-1-carboxymethyl-2,3-dihydro-5-phenyl-1H-1,4-benzodiazepin-2-one, (N-Me)BZA, shown below.
authors.affiliation: Department of Bioorganic Chemistry, Genentech, Inc., South San Francisco, CA.
authors.forename: J C
authors.initials: JC
authors.lastname: Marsters
authors.forename: T E
authors.initials: TE
authors.lastname: Rawson